Timolol (Systemic use) is a non-selective beta-receptor blocker that does not have intrinsic sympathomimetic activity.
Indications of Timolol:
-
Hypertension:
- It is used for the management of hypertension.
Note: According to (ACC/AHA [Whelton 2017]) Beta-blockers are no longer the first-line treatment of hypertension.
-
Migraine prophylaxis:
- It is indicated as a prophylaxis of migraine.
-
As secondary prevention in Myocardial Infarction
- It is shown to reduce mortality in patients with myocardial infarction.
-
Timolol use in Adults ( Off Label )
- Timolol is effective as a rate controlling agent in atrial fibrillation.
Timolol dose in adults:
Treatment dose as alternative agent for hypertension:
- Initial: 10 mg per oral b.i.d daily; adjust dose based on patient response at intervals of at least every 7 days.
- usual dosage: 20 to 40 mg/day in 2 divided doses.
- maximum: 60 mg/day.
Timolol Dose in the prophylaxis of Migraine:
- Initial:10mg per oral in two divided doses.
- Maximum:30mg/day in 2 divided doses.
Treatment dose of Myocardial infarction (secondary prevention):
- Initial:5 mg per oral b.i.d daily and titrated up to a required dose of 10mg two times a day.
- It should be started within a day after a Myocardial event( STEMI) and should be given life long.
- It is not recommended in case of any contraindication.
- Timolol is not frequently used.
Timolol Treatment dose of Atrial fibrillation (rate control) (off-label):
- Initial: 10 mg per oral b.i.d daily;
- increase at weekly intervals as tolerated to 20 mg twice daily.
- The Maximum dose is 30 mg twice daily;
- may use in combination with digoxin.
Timolol use in Children:
Not indicated in Children.
Pregnancy Risk Factor C
- Studies on animal reproduction did not show any adverse outcomes.
- Timolol can cross placenta.
- When timolol (used by mothers during pregnancy) is administered, a decreased fetal heart beat is observed.
- Beta-blockers have been shown to cause adverse effects in utero, including low birth weight and fetal/neonatal hyperglycemia.
- It is therefore important to monitor your baby closely after it has been born.
- If preeclampsia and chronic maternal hypertension are not treated, adverse events can occur in the mother, infant, or both.
- For treating pregnancy hypertension, alternative beta-blockers are more effective than timolol.
- For migraine prophylaxis in pregnancy, it is better to use alternative agents than timolol.
Timolol use during breastfeeding:
- Breast milk contains Timolol.
- After maternal use of ophthalmic-timolol, it is important to monitor breastfeeding infants for adverse effects.
- The manufacturer suggests that the mother decide whether to stop breastfeeding her infant or if the drug should be used.
- This decision will depend on how important the mother is to her health.
Timolol Dose adjustment in renal disease:
- There are no specific dosage adjustments provided in the manufacturer’s labeling.
- However, dose reduction is necessary as timolol is primarily eliminated renally.
- Caution should be exercised as significant hypotension has been seen in patients with severe impairment and undergoing dialysis.
Timolol Dose adjustment in Liver disease:
- There are no specific dosage adjustments provided in the manufacturer’s labeling.
- Dose reduction is required in hepatic impairment as timolol is partially metabolized by the liver.
Side Effects of Timolol:
-
Cardiovascular:
- Bradycardia
-
Central Nervous System:
- Dizziness
- Fatigue
-
Respiratory:
- Dyspnea
Uncommon Side effects of Timolol:
-
Cardiovascular:
- Angina Pectoris
- Cardiac Arrhythmia
- Cardiac Failure
- Cerebral Ischemia
- Cerebrovascular Accident
- Claudication
- Cold Extremities
- Edema
- Heart Block
- Hypotension
- Palpitations
- Raynaud's Phenomenon
-
Central Nervous System:
- Amnesia
- Anxiety
- Confusion
- Depression
- Disorientation
- Drowsiness
- Exacerbation Of Myasthenia Gravis
- Hallucination
- Insomnia
- Nervousness
- Nightmares
- Paresthesia
-
Dermatologic:
- Alopecia
- Exacerbation Of Psoriasis
- Pemphigoid-Like Lesion
- Psoriasiform Eruption
- Skin Rash
- Urticaria
-
Endocrine & Metabolic:
- Decreased Libido
- Hypoglycemia (Masked)
-
Gastrointestinal:
- Anorexia
- Diarrhea
- Dyspepsia
- Nausea
- Xerostomia
-
Genitourinary:
- Impotence
- Peyronie's Disease
- Retroperitoneal Fibrosis
-
Hypersensitivity:
- Angioedema
- Hypersensitivity Reaction
-
Neuromuscular & Skeletal:
- Systemic Lupus Erythematosus
-
Ophthalmic:
- Blepharoptosis
- Cystoid Macular Edema
- Decreased Corneal Sensitivity
- Diplopia
- Eye Discharge
- Eye Pain
- Keratitis
- Visual Disturbance (Including Refractive Changes)
- Xerophthalmia
-
Otic:
- Tinnitus
-
Respiratory:
- Bronchospasm
- Cough
- Nasal Congestion
- Pulmonary Edema
- Respiratory Failure
Contraindications to Timolol:
- Hypersensitivity to timolol and any component of the formulation
- Sinus bradycardia
- Cardiogenic shock
- Uncompensated cardiac Failure
- Patients without an artificial pacemaker that is not functioning properly have a heart block of greater severity than the first.
- Bronchospastic Disease
- There is not much evidence of cross-reactivity between beta-blockers and allergenic beta-blockers.
- Cross-sensitivity is possible due to similarities in chemical structure and/or drugcologic actions. However, this cannot be ruled out.
Canadian labeling: Additional contraindications not in US labeling
- Allergy rhinitis
- Severe COPD
- Important cardiomegaly
- Right ventricular failure due to pulmonary hypertension anesthesia using agents that cause myocardial depression (eg ether hypersensitivity for timolol malate).
Warnings and precautions
-
Anaphylactic reactions
- Patients with severe allergic reactions to allergens should be cautious when using beta-blockers. They can become more sensitive to repeated challenges.
- In patients using beta-blockers, the treatment of anaphylaxis (eg, epinephrine)can be ineffective.
-
Bronchospastic disease
- Patients with bronchospastic diseases should not take beta-blockers.
- It should only be used if it is absolutely necessary.
-
Conductive abnormality
- Pre-existing conditions like sick sinus syndrome must be checked before you start beta-blocker treatment.
-
Diabetes:
- Patients with diabetes mellitus should be cautious when taking beta-blockers. They can lead to hypoglycemia, or mask signs and symptoms associated with diabetic complications.
-
Heart failure:
- Patients with compensated cardiac failure require careful monitoring and caution.
-
Myasthenia gravis:
- Beta-blockers have been shown to make myasthenia gravis worse, so it is important to be cautious with such patients.
-
Raynaud and peripheral vascular disease:
- Patients with Raynaud disease or peripheral vascular disease can experience symptoms of arterial insufficiency. To detect any signs or symptoms that are getting worse, it is important to keep your condition under close observation.
-
Untreated Pheochromocytoma
- A sufficient alpha-blockade in the case of pheochromocytoma is required before any beta-blocker can be used.
-
Angina Prinzmetal version:
- Patients with prinzmetal variant Angina should not receive beta-blockers that do not block alpha1 receptors.
-
Psoriasis:
- Beta-blocker therapy can be used to exacerbate or induce psoriasis, but the cause and effect of this treatment are not known.
-
Renal impairment
- Extreme caution is necessary for patients suffering from severe renal impairment.
- Patients on dialysis may experience severe hypotension.
-
Thyroid disease:
- Beta-blockers can mask certain signs of hyperthyroidism, such as tachycardia. If thyrotoxicosis suspects are advised to monitor closely.
- Sudden withdrawal of therapy can lead to symptoms of hyperthyroidism and precipitation of thyroid storm.
Timolol (systemic): Drug Interaction
|
Acetylcholinesterase Inhibitors |
May enhance the bradycardic effect of Beta-Blockers. |
|
Ajmaline |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Alpha1-Blockers |
Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1Blockers. The risk associated with ophthalmic products is probably less than systemic products. |
|
Aminoquinolines (Antimalarial) |
May decrease the metabolism of Beta-Blockers. |
|
Amiodarone |
May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. |
|
Amphetamines |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Antipsychotic Agents (Phenothiazines): |
May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Barbiturates |
May decrease the serum concentration of Beta-Blockers. |
|
Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bradycardia-Causing Agents |
May enhance the bradycardic effect of other Bradycardia-Causing Agents. |
|
Bretylium |
May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. |
|
Brigatinib |
May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. |
|
Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bupivacaine |
Beta-Blockers may increase the serum concentration of Bupivacaine. |
|
Calcium Channel Blockers (Nondihydropyridine) |
May enhance the hypotensive effect of BetaBlockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. |
|
Cardiac Glycosides |
Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. |
|
Cholinergic Agonists |
Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. |
|
CloBAZam |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Cobicistat |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
CYP2D6 Inhibitors (Moderate) |
May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). |
|
Darunavir |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dipyridamole |
May enhance the bradycardic effect of Beta-Blockers. |
|
Disopyramide |
May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
EPINEPHrine (Nasal) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). |
|
EPINEPHrine (Oral Inhalation) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). |
|
Epinephrine (Racemic) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). |
|
EPINEPHrine (Systemic) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). |
|
Herbs (Hypertensive Properties) |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Imatinib |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Insulins |
Beta-Blockers may enhance the hypoglycemic effect of Insulins. |
|
Ivabradine |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. |
|
Lacosamide |
Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Lidocaine (Systemic) |
Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). |
|
Lidocaine (Topical) |
Beta-Blockers may increase the serum concentration of Lidocaine (Topical). |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Lumefantrine |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Mepivacaine |
Beta-Blockers may increase the serum concentration of Mepivacaine. |
|
Methoxyflurane |
May enhance the hypotensive effect of Beta-Blockers. |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Midodrine |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
NIFEdipine |
May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Nonsteroidal Anti-Inflammatory Agents |
May diminish the antihypertensive effect of BetaBlockers. |
|
Opioids (Anilidopiperidine) |
May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. |
|
Panobinostat |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Peginterferon Alfa-2b |
May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Perhexiline |
CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Propafenone |
May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
QuiNINE |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Regorafenib |
May enhance the bradycardic effect of Beta-Blockers. |
|
Reserpine |
May enhance the hypotensive effect of Beta-Blockers. |
|
Rifamycin Derivatives |
May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. |
|
Ruxolitinib |
May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. |
|
Selective Serotonin Reuptake Inhibitors |
May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. |
|
Sulfonylureas |
Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. |
|
Terlipressin |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Tofacitinib |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Abiraterone Acetate |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. |
|
Alpha2-Agonists |
May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. |
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Asunaprevir |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Ceritinib |
|
|
CYP2D6 Inhibitors (Strong) |
May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). |
|
Dacomitinib |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. |
|
Dronedarone |
May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in betablocker dose. |
|
Ergot Derivatives |
Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. |
|
Fingolimod |
Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. |
|
Grass Pollen Allergen Extract (5 Grass Extract) |
Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Siponimod |
Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. |
|
Theophylline Derivatives |
Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. |
|
Risk Factor X (Avoid combination) |
|
|
Beta2-Agonists |
Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2Agonists. |
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Floctafenine |
May enhance the adverse/toxic effect of Beta-Blockers. |
|
Methacholine |
Beta-Blockers may enhance the adverse/toxic effect of Methacholine. |
|
Rivastigmine |
May enhance the bradycardic effect of Beta-Blockers. |
Monitoring parameters:
- BP
- Heart rate
- Apical and radial pulses
Hypertension:
- The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults:
Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
- Target blood pressure <130/80 mm Hg is recommended.
Confirmed hypertension without markers of increased ASCVD risk:
- Target blood pressure <130/80 mm Hg may be reasonable.
How to administer Timolol?
It should be given orally with food at the same time each day.
Mechanism of action of Timolol:
- It works by blocking both beta-adrenergic and beta-adrenergic receptors.
- It works by decreasing sympathetic outflow and blocking adrenergic receptors, which in turn lowers blood pressure.
- It produces negative inotropic and chronotropic activity through an unknown mechanism.
The onset of action:
- Hypotensive: 15 to 45 minutes.
Peak effect:
- 0.5 to 2.5 hours.
Duration:
- 4 hours.
Absorption:
- Rapid and complete (90%).
Protein binding:
- 60%.
Metabolism:
- Extensively hepatic via CYP2D6; extensive first-pass effect.
Bioavailability:
- 50%.
Half-life elimination:
- 2 to 2.7 hours; prolonged with renal impairment.
Time to peak, plasma:
- 1 to 2 hours.
Excretion:
- Urine (15% to 20% as unchanged drug).
International Brands of Timolol:
- Arutimol
- Blocadren
- Blocadren Depot
- Normatin
Timolol Brands in Pakistan (Systemic and Ophthalmic):
Timolol Injection 5 mg/10ml |
|
| Millisrol | S. Ejazuddin & Company |
Timolol Maleate Eye Drops 0.5 %w/v |
|
| Altim | Jaens Pharma |
| Betalol | Sante (Pvt) Limited |
| Blotim | Remington Pharmaceutical Industries (Pvt) Ltd. |
| Dytim | Azron Pharmaceuticals (Pvt) Ltd |
| Meditim | Medipak Limited |
| Milosol | Polyfine Chempharma (Pvt) Ltd. |
| Nyolol | Novartis Pharma (Pak) Ltd |
| Ocutim | Farmigea Pak (Pvt) Ltd. |
| Optipress | Ethical Laboratories (Pvt) Ltd. |
| Tiloptic | Mascon Pharmacal |
| Timentin Drops | Atco Laboratories Limited |
| Timo Stulln Ud | Haroon Brothers |
| Timo Stulln Ud | Haroon Brothers |
| Timol | Panacea Pharmaceuticals |
| Timoptic | Helix Pharma (Private) Limited |
| Timoptol | Obs |
| Timorex | Vega Pharmaceuticals Ltd. |
| Timosol | The Schazoo Laboratories Ltd. |
| Timotek | Innvotek Pharmaceuticals |
Timolol Maleate Eye Drops 0.25 %w/v |
|
| Blotim | Remington Pharmaceutical Industries (Pvt) Ltd. |
| Hioptol | Himont Pharmaceuticals (Pvt) Ltd. |
| Ocotimol | Ocu Care |
| Optipress | Ethical Laboratories (Pvt) Ltd. |
| Timoptol | Obs |
.png)
